Chloride electrodiffusion across the apical membrane of granular cells from toad urinary bladder, an analogue of mammalian principal cells, was examined using the patch clamp technique. A chloride conductance was demonstrated in cell-attached membrane patches exposed to barium chloride pipette solutions. A change in the pipette chloride concentration from 30 to 100 mM caused a shift in the current voltage curve which demonstrated chloride selectivity. The chloride conductance was also examined in excised, inside out membrane patches using choline chloride solutions (chloride:choline selectivity ratio was 18:1). A closed and two open chloride conductive states were found (states A and B, 10.1 +/- 1.0 and 17.2 +/- 5.5 pS, respectively, p < 0.01). Incubation of the preparation with arginine vasopressin, dibutyryl-cAMP, or 8-bromo-cAMP approximately doubled chloride conductance to 16.6 +/- 1.7 pS (p < 0.01). The enhanced electrodiffusion was accounted for by a shift in the channel kinetics from the closed state C to the high conductance state B (p < 0.05, n = 9). 4,4'-Diisothio-cyanatostilbene- 2,2'-disulfonic acid (DIDS) and 9-anthracene-carboxylic acid (9-AC) failed to block the chloride currents. In conclusion, the regulated apical chloride conductance described would balance the sodium and potassium electrodiffusive pathways and maintain a stable membrane potential, facilitating overall conductive transport by these cells.